Process for preparing 7H-pyrrolo[2,3-d]pyrimidine derivatives and co-crystals thereof
The present invention relates to processes for preparing 7H-pyrrolo[2,3-d]pyrimidine derivatives which are useful as a Janus kinase (JAK) inhibitor, co-crystals thereof, processes for preparing the co-crystals, and processes for purifying 7H-pyrrolo[2,3-d]pyrimidine derivatives by employing the co-crystals. The present invention provides, for example, a process for preparing 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile by employing a co-crystal of 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile with 3,5-dimethylpyrazole.
1. A co-crystal of 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile with 3,5-dimethylpyrazole.
2. The co-crystal of claim 1 , having the structure of formula [3a]
wherein m is any number of 0.4 to 0.5.
3. The co-crystal of claim 2 , wherein m is 0.5.
4. The co-crystal of claim 1 , showing an extrapolated onset temperature of 172±5° C. in differential scanning calorimetry.
5. The co-crystal of claim 1 , showing a X-ray powder diffraction pattern having at least one peak at 4.6°±0.2°, 18.6°±0.2° or 20.9°±0.2° of a diffraction angle (2θ)) measured by using CuKα radiation.
6. The co-crystal of claim 1 , showing a X-ray powder diffraction pattern having at least one peak at 4.6°±0.2°, 12.6°±0.2°, 16.1°±0.2°, 18.6°±0.2° or 20.9°±0.2° of a diffraction angle (2θ)) measured by using CuKα radiation.
7. A process for preparing a compound of formula [4]
or its salt by employing the co-crystal of claim 1 .
8. The process of claim 7 , further comprising the step of reacting a compound of formula [1]
or its salt with a compound of formula [2]
to give a compound of formula [4] or its salt.
9. A process for purifying a compound of formula [4]
or its salt by employing the co-crystal of claim 1 .
10. The process of claim 9 , further comprising the step of reacting a compound of formula [1]
or its salt with a compound of formula [2]
to give a compound of formula [4] or its salt.
11. A process for preparing a co-crystal having the structure of formula [3a]
wherein m is any number of 0.4 to 0.5, comprising the step of reacting a compound of formula [1]
or its salt with a compound of formula [2]
to give the co-crystal of formula [3a].
12. A process for preparing a co-crystal having the structure of formula [3a]
wherein m is any number of 0.4 to 0.5, comprising the step of reacting a compound of formula [4]
or its salt with a compound of formula [5]
to give the co-crystal of formula [3a].
13. The process of claim 11 , wherein m is 0.5.
14. The process of claim 11 , wherein the co-crystal of formula [3a] shows an extrapolated onset temperature of 172±5° C. in differential scanning calorimetry.
15. The process of claim 11 , wherein the co-crystal of formula [3a] shows a X-ray powder diffraction pattern having at least one peak at 4.6°±0.2°, 18.6°±0.2° or 20.9°±0.2° of a diffraction angle (2θ) measured by using CuKα radiation.
16. The process of claim 11 , wherein the co-crystal of formula [3a] shows a X-ray powder diffraction pattern having at least one peak at 4.6°±0.2°, 12.6°±0.2°, 16.1°±0.2°, 18.6°±0.2° or 20.9°±0.2° of a diffraction angle (2θ)) measured by using CuKα radiation.